In a recent study published in The New England Journal of Medicine, researchers conducted the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) trial to determine whether long-term oral beta-blocker therapy could reduce the risk of any cause or incident MI-related mortality among individuals with acute myocardial infarction but preserved left ventricular ejection fraction compared to no beta-blocker treatment.
Study: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. Image Credit: aipicte / Shutterstock
Background
Beta-blockers are beneficial in treating heart failure patients and those with reducing ejection fractions; however, these findings are from 1980s trials of patients with massive myocardial infarctions and systolic dysfunction in the left ventricle. Meta-analytical research indicated that beta-blockers do not appear to lower mortality in contemporary reperfusion techniques.
There is a lack of data from recent randomized clinical studies on the efficacy of long-term use of beta-blockers among acute myocardial infarction patients with intact ejection fraction. Previous Cochrane reviews underscore the need for novel research studies in this target population. Despite the absence of convincing scientific evidence of medication benefit, current recommendations strongly advocate beta-blocker therapy following a myocardial infarction.
About the study
In the present open-label, prospective, parallel-group trial, researchers evaluated the impact of beta-blocker therapy on reducing mortality among acute MI patients.
The team conducted the registry-based trial between September 2017 and May 2023 at 45 sites across New Zealand, Sweden, and Estonia. They randomized participants with prior acute MI who underwent coronary angiographies and had ≥50% ejection fraction from the left ventricle to receive 1:1 long-term therapy with beta-blockers such as ≥100 mg/day of metoprolol or ≥5 mg/day of bisoprolol (intervention group) or no such therapy.
All participants had obstructive coronary heart disease, as determined from coronary angiographies (i.e., ≥50% stenosis, ≤0.8 fractional flow reserves, or ≤0.9 instant wave-free segment ratios) before randomization. The primary outcome was the composite measure of all-cause or incident MI-related mortality. Secondary outcomes included cardiovascular disease-related mortality and hospital admission for atrial fibrillations or heart failure.
Safety outcomes included hospital admission for hypotension, second and third-degree atrioventricular blocks, bradycardia, syncope, or pacemaker implantation, and hospital admission due to chronic obstructive pulmonary disease (COPD), asthma, or stroke. Other endpoints included dyspnea [diagnosed using the New York Heart Association (NYHA) recommendations] and angina pectoris (diagnosed using the Canadian Cardiovascular Society guidelines) six to 10.0 weeks or 11.0 to 13.0 months after treatment. The team used Cox proportional-hazards regressions to determine the hazard ratios (HR) for analysis. They performed sensitivity analyses, adjusting for age, country, diabetes, and prior myocardial infarction. The Swedish population registry provided data on death or emigration, and the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) register collected data on incident myocardial infarctions. The national cause-of-death registry provided cardiovascular-related mortality data, while the national patient registry provided data on atrial fibrillation, heart failure, and safety outcomes.
Results
The researchers enrolled 5,020 MI patients (95% from Sweden) who followed up for a median of 3.50 years until November 16, 2023. The median participant age was 65.0 years, 23% were female, and 35% had myocardial infarction with an elevation in the ST segment. Among the participants, 46% were hypertensive, 14% were diabetic, and 7.1% had a prior myocardial infarction. Of 2,508 beta-blocker recipients, 1,560 (62%) and 948 (38%) received metoprolol and bisoprolol, respectively.
Coronary angiography showed one-vessel involvement among 55% of MI patients, two vessels involved among 27%, and three vessels involved among 17% of patients. The team performed percutaneous coronary interventions in 96% of patients, with coronary artery bypass grafting (CABG) among 3.9%. At hospital discharge, 97% received aspirin, P2Y12 receptor blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins.
The researchers observed the primary endpoint among 7.9% (199 out of 2,508) of beta-blocker recipients and 8.3% (208 out of 2,512) of non-recipients (HR, 0.96). Beta-blockers did not lower the cumulative incidence rates of secondary endpoints (all-cause mortality, 3.90% and 4.10% among beta-blocker recipients and non-recipients, respectively); cardiovascular disease-related mortality, 1.50% and 1.30%, respectively; myocardial infarctions, 4.50% and 4.70%; hospital admission due to atrial fibrillations, 1.10% and 1.40%; and hospital admission due to heart failures, 0.80% and 0.90%).
Concerning safety endpoints, the researchers observed hospital admission due to atrioventricular blocks, bradycardia, syncope, hypotension, or pacemaker implantation among 3.40% of beta-blocker recipients and 3.20% of non-recipients; hospital admission due to COPD or asthma in 0.60% and 0.60%, respectively, and hospital admission due to stroke among 1.40% and 1.80% of beta-blocker recipients and non-recipients, respectively. Subgroup analyses yielded similar results.
Overall, the study findings showed that long-term use of beta-blockers did not reduce the risk of all-cause or incident myocardial infarction-related mortality in patients with an acute MI who underwent coronary angiography but retained ≥50% ejection fraction from the left ventricle compared to no treatment with beta-blockers.
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